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Opioid Addiction Medication Could Bring Relief to Long COVID Patients

White pharmaceutical drugs in a clear orange bottle
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Long COVID has become a major public health issue, with 37% of individuals reporting one or more long COVID symptoms in the 3 to 6 months after their COVID-19 diagnosis.

Symptoms of long COVID can include brain fog, muscle fatigue and issues with the cardiovascular and gastrointestinal systems.  There is currently no universal treatment for long COVID but new findings from researchers at Griffith University’s National Centre for Neuroimmunology and Emerging Diseases (NCNED) suggest that the addiction medication naltrexone (NTX) could bring relief to those struggling with long COVID.

The findings were published in the journal Frontiers in Immunology.

A promising treatment for chronic fatigue

The study builds on previous research that showed long COVID patients share similar issues with immune cell ion channels as those with chronic fatigue syndrome, also known as myalgic encephalomyelitis or ME/CFS.

ME/CFS etiology has been associated with immune system dysfunction, reduced natural killer (NK) cell cytotoxic activity, impaired calcium mobilization and transient receptor potential melastatin 3 (TRPM3) ion channel dysfunction.

TRPM3 is a non-selective ion channel highly permeable to calcium ions and broadly expressed in the human body. The contribution of TRPM3 in the regulatory function of calcium ion homeostasis is vital to processes such as cell signaling. TRP ion channels may also facilitate host–viral interactions through calcium ion regulation and may promote viral pathogenesis during SARS-CoV-2 infection.

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Past research has shown that NTX is beneficial as a pharmacological intervention for ME/CFS patients with experimental investigations showing it to restore TRPM3 function in NK cells.

Given the link between ME/CFS and long COVID, the researchers set out to validate impaired ion channel function in long COVID patients compared with ME/CFS. They also investigated the effects of naltrexone on these ion channels.

What is naltrexone?

Naltrexone is an FDA-approved opioid antagonist used to treat alcohol use disorder and opioid dependence. It is a μ-opioid receptor antagonist that negates the inhibitory function on TRPM3 ion channels.

The investigation confirmed impaired TRPM3 function in NK cells from long COVID and ME/CFS patients. This consequently results in disturbed calcium signaling and cell homeostasis in both diseases. These findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and long COVID patients.

The study also reports, for the first time, that TRPM3 ion channel activity was restored in NK cells isolated from long COVID patients after in vitro treatment with NTX facilitating calcium influx for intracellular signaling pathways.

The authors state: “This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.”

The NCNED is now preparing to launch two clinical trials, one for long COVID and another for ME/CFS, testing the effectiveness of low-dose NTX. The drug has shown promising results in restoring ion channel function in previous research and anecdotal reports from patients.

“We will be undertaking two clinical trials testing the efficacy of low dose naltrexone where the first will be in Long COVID patients while the second trial will, for the first time, be in ME/CFS patients,” said Professor Sonya Marshall-Gradisnik, senior author and director of NCNED.

“Should these trials prove successful, it could mean a vastly improved quality of life for countless individuals struggling with Long COVID and ME/CFS.”

Reference:  Sasso EM, Muraki K, Eaton-Fitch N, et al. Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target. Front Immunol. 2024;15. doi: 10.3389/fimmu.2024.1264702

This article is a rework of a press release issued by Griffith University. Material has been edited for length and content.